Medicaments for inhalation comprising steroids and an anticholinergic

• US 20060069073A1
• Filed: 06/27/2005
• Published: 03/30/2006
• Est. Priority Date: 06/29/2004
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pairet, Michel, Pieper, Michael P.
• Application Number:
  US11/168,619
• Publication Number:
  US 20060069073A1
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics

Abstract

The present invention relates to novel pharmaceutical compositions based on steroids and salts of an anticholinergic, processes for preparing them and their use in the treatment of respiratory complaints.

Claims

1. A Pharmaceutical composition, which comprises as a first active substance one or more salts of formula 1

2. The pharmaceutical composition of claim 1 wherein the second active substance is selected from the group consisting of methyl prednisolone, prednisone, butixocort propionate, RPR-106541, flunisolide, triamcinolone, budesonide, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, 6α

,9α

-difluoro-17α

-[(2-furanylcarbonyl)oxy]-11β

-hydroxy-16α

-methyl-3-oxo-androsta-1,4-diene-17β

-carbothioic acid (S)-fluoromethyl ester, 6α

,9α

-difluoro-11β

-hydroxy-16α

-methyl-3-oxo-17α

-propionyloxy-androsta-1,4-diene-17β

-carbothioic acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester, and etiprednol, optionally in the form of the stereoisomers, mixtures of the stereoisomers or in the form of the racemates thereof, optionally in the form of the solvates or hydrates.

3. The pharmaceutical composition according to claim 1, characterised in that the first active substance and the second active substance are present together in a single formulation or in two separate formulations.

4. The pharmaceutical composition according to claim 1, characterised in that the compounds of formula 1 are present in form of the (3S,2′

R)-diasteromer, in form of the (3S,2′

S)-diasteromer, in form of the (3R,2′

S)-diasteromer or in form of the (3R,2′

R)-diasteromer.

5. The pharmaceutical composition according to claim 2, characterised in that the second active substance steroid is selected from the group consisting of flunisolide, triamcinolone, budesonide, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, 6α

,9α

-difluoro-17α

-[(2-furanylcarbonyl)oxy]-11β

-hydroxy-16α

-methyl-3-oxo-androsta-1,4-diene-17β

-carbothioic acid (S)-fluoromethyl ester, 6α

,9α

-difluoro-11β

-hydroxy-16α

-methyl-3-oxo-17α

-propionyloxy-androsta-1,4-diene-17β

-carbothioic acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester, and etiprednol.

6. The pharmaceutical composition according to claim 5, characterised in that the second active substance steroid is selected from the group consisting of budesonide, mometasone, ciclesonide, 6α

,9α

-difluoro-17α

-[(2-furanylcarbonyl)oxy]-11β

-hydroxy-16α

-methyl-3-oxo-androsta-1,4-diene-17β

-carbothioic acid (S)-fluoromethyl ester, and etiprednol.

7. The pharmaceutical composition according to claim 1, characterised in that the weight ratios of first active substance to second active substance are in a range from about 1:

250 to 250;

1.

8. The pharmaceutical composition according to claim 1, characterised in that it is in the form of a preparation suitable for inhalation.

9. The pharmaceutical composition according to claim 8, characterised in that it is a preparation selected from among the inhalable powders, propellant-containing metered-dose aerosols and propellant-free inhalable solutions.

10. The pharmaceutical composition according to claim 9, characterised in that it is an inhalable powder which comprises the first active substance and the second active substance in admixture with suitable physiologically acceptable excipients selected from among the monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, salts, or mixtures of these excipients with one another.

11. The pharmaceutical composition according to claim 10, characterised in that the excipient has a maximum average particle size of up to 250 μ

m.

12. The pharmaceutical composition according to claim 9, characterised in that it is an inhalable powder which consists of only the first active substance and the second active substance as its ingredients.

13. The pharmaceutical composition according to claim 9, characterised in that it is a propellant-containing inhalable aerosol which contains the first active substance and the second active substance in dissolved or dispersed form.

14. The pharmaceutical composition according to claim 13, characterised in that it comprises as propellant gas hydrocarbons, such as n-propane, n-butane or isobutene, or halohydrocarbons, such as chlorinated and/or fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane.

15. The pharmaceutical composition according to claim 14, characterised in that the propellant gas is TG11, TG12, TG134a, TG227 or mixtures thereof.

16. The pharmaceutical composition according to claim 9, characterised in that it is a propellant-free inhalable solution which comprises water, ethanol or a mixture of water and ethanol as solvent.

17. The pharmaceutical composition according to claim 16, characterised in that it comprises as co-solvents ingredients which contain hydroxyl groups or other polar groups, e.g. alcohols—

particularly isopropyl alcohol, glycols—

particularly propyleneglycol, polyethyleneglycol, polypropyleneglycol, glycolether, glycerol, polyoxyethylene alcohols and polyoxyethylene fatty acid esters.